Researchers at the University of Pennsylvania have found that men who take hormone-blocking therapy for prostate cancer may be at an increased risk for developing dementia and Alzheimer’s disease, compared with patients who do not receive the treatment.
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In a study involving 154,089 elderly men who were newly diagnosed with prostate cancer between1996 and 2003, those who received androgen-deprivation therapy were at 20% greater risk of being diagnosed with dementia and a 14% greater risk of being diagnosed with Alzheimer’s over the following ten years. The risk of being diagnosed with the conditions continued to rise, the greater the dose of therapy the men received.
Prostate cancer patients who take drugs to block the androgen that fuels tumor growth can suffer a range of side effects including bone loss, heart problems, obesity and impotence. Other common side effects include mood swings, difficulty sleeping, headaches, hot flashes and high blood sugar.
Now, a study by Ravishankar Jayadevappa and colleagues suggests that an increased risk for dementia is another potential downside to treatment.
Jayadevappa says the findings suggest that in cases where the cancer is localized, administering androgen-deprivation therapy may not be the best choice and that even high-risk patients need to be warned about the increased risk for the conditions.
The researchers note that so far studies into the cognitive effects associated with the therapy have generated mixed results. In an attempt to produce more definitive findings, Jayadevappa and team used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results–Medicare linked database. The database holds information on cancer incidence, therapy and death from 18 sites across the U.S. and links it with Medicare data.
Themen, who were aged 66 and older, had been diagnosed with localized or metastasized prostate cancer between 1996 and 2003 and were followed until 2013, so all men had been assessed over at least ten years.
Of all the men included in the study, 62,330 had been given androgen deprivation therapy within two years of receiving a diagnosis.
Over the follow-up period, 13.1% of percent of those who received the therapy were diagnosed with Alzheimer’s compared with 9.4% of those who did not receive it. Similarly, 21.6% of those who received the therapy were diagnosed with other types of dementia, compared with 15.8% of those who did not.
The risk for the conditions also increased the greater the exposure to the therapy; men who received up to four doses were at a 19% greater risk for either condition, while those who received eight or more doses were at a 24% greater risk for Alzheimer’s and a 21% greater risk for dementia.
Researchers are calling for Androgen Deprivation Therapy (ADT) to be used as a last resort
Catherine Marshall, assistant professor at Johns Hopkins in Baltimore, Maryland welcomes the study, saying:
While this question of a link between ADT and Alzheimer's disease and dementia has been explored before, this is quite possibly the largest study to address this issue. Because of that, it adds important information about the risk of Alzheimer's disease and dementia for men being treated."
Writing in JAMA Network Open, Jayadevappa and colleagues say clinicians must carefully weigh the long-term risks and benefits of exposure to androgen deprivation therapy in patients with a prolonged life expectancy and stratify patients by dementia risk prior to androgen deprivation therapy initiation.
"Delaying the start of ADT until the disease is more advanced may be a reasonable option for many men and would help to ultimately shorten the total duration of treatment,” adds Marshall.
Last month, research fellows at Brigham and Women's Hospital in Boston, Karl Tully and colleagues presented similar findings at the American Urological Association annual meeting, in Chicago.
For that study, the team gathered data available for more than 100,400 men enrolled in Medicare who had been diagnosed with prostate cancer between January 1992 and December 2009.
Tully and team found that men who received androgen deprivation therapy were at a 17% increased risk for any type of dementia, and a 23% increased risk for Alzheimer’s.
Androgen-deprivation therapy may not only cause physical changes such as osteoporosis, cardiovascular disease or obesity, but may also cause changes in cognition… physicians should be telling their patients about that risk and should probably perform regular screening."
Karl Tully, Brigham and Women's Hospital
The decision to delay ADT should not be taken lightly
However, urology specialist Elizabeth Kavaler from Lenox Hill Hospital in New York City does not think patients need to be told about the association because she thinks the increase in dementia incidence may not have been due to the therapy and that many of the patients may have had other health problems that could have increased their risk for dementia.
She also notes that many patients with prostate cancer may not have any alternative:
"We really don't have a choice. Androgen-deprivation therapy is what can be offered to men with recurring or advanced prostate cancer. It's a matter of treating a deadly disease versus the risk of developing a non-life-threatening condition."
"How do you ask somebody to choose between losing your mind or not treating their high-risk disease. It's a hard position to put a patient in. I wouldn't even bring it up."
Jayadevappa also thinks that in cases of advanced cancer, the therapy can be a lifesaving treatment and should not be avoided due to fears of any increased risk for dementia. However, “patients with localized cancer should be looking at the risks of dementia, and possibly avoiding A.D.T,” he concludes.
Jayadevappa R, Chhatre S, Malkowicz SB, Parikh RB, Guzzo T, Wein AJ. Association Between Androgen Deprivation Therapy Use and Diagnosis of Dementia in Men With Prostate Cancer. JAMA Netw Open. 2019. doi:10.1001/jamanetworkopen.2019.6562.